NDA Submitted for Cabozantinib for Medullary Thyroid Cancer

Exelixis announced that it has completed the filing of its rolling New Drug Application (NDA) with the FDA for cabozantinib as a treatment for patients with progressive, unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC).

The NDA was submitted under the FDA's Fast Track designation, which is designed to potentially accelerate the review of an investigational therapy for an unmet medical need. As part of the NDA filing, Exelixis has requested Priority Review designation from the FDA. If granted, the FDA's goal for completing the review would be six months from the date of receipt of the final submission.

The NDA filing is based on data from the EXAM trial, a Phase 3 pivotal trial in patients with advanced MTC. The trial was conducted under a Special Protocol Assessment with the FDA, with progression-free survival (PFS) as the primary endpoint. In October 2011, Exelixis announced top-line results from EXAM demonstrating that the trial had met its primary endpoint of improving PFS: compared with placebo, cabozantinib improved median PFS by 7.2 months. The median PFS on the cabozantinib arm was 11.2 months vs. 4 months on the placebo arm, with a hazard ratio (HR) of 0.28, (95% CI 0.19, 0.4), P< 0.0001.

Cabozantinib is a potent inhibitor of MET, RET and VEGFR2 that inhibits tumor growth, metastasis and angiogenesis in preclinical models. MET is up-regulated in many tumor types, and promotes tumor cell survival, invasion and metastasis. Further up-regulation of MET occurs under hypoxic conditions, which are often exacerbated by VEGF-pathway inhibitors, promoting increased tumor cell invasion and metastases. Activation of RET is a frequent occurrence in both medullary and papillary thyroid cancers. The therapeutic role of cabozantinib is currently being investigated across multiple tumor types.